Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition

Abstract

Aims Hydrogen sulfide (H 2S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H 2S on vascular tone. Main methods We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H 2S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues. Key findings We have found that in rat aortic rings: (1) H 2S decreases ATP levels; (2) relaxations to H 2S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H 2S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP)–nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of K ATP channels is limited, while Cl −/HCO 3 − channels have a role in the relaxations. (6): We have observed that high concentrations of H 2S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree. Significance H 2S, a new gasotransmitter of emerging importance, leads to relaxation via Cl −/HCO 3 − channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue.